Susan S. Percival

Moderate consumption of Cabernet Sauvignon attenuates Aβ neuropathology in a mouse model of Alzheimer’s disease

Recent studies suggest that moderate red wine consumption reduces the incidence of Alzheimers disease (AD) clinical dementia. Using Tg2576 mice, which model AD‐type amyloid beta‐protein (Aβ) neuropathology, we tested whether moderate consumption of the red wine Cabernet Sauvignon modulates AD‐type neuropathology and cognitive deterioration. The wine used in the study was generated using Cabernet Sauvignon grapes from Fresno, California, and was delivered to Tg2576 in a final concentration of ~6% ethanol. We found that Cabernet Sauvignon significantly attenuated AD‐type deterioration of spatial memory function and Aβ neuropathology in Tg2576 mice relative to control Tg2576 mice that were treated with either a comparable amount of ethanol or water alone. Chemical analysis showed the Cabernet Sauvignon used in this study contains a very low content of resveratrol (0.2 mg/L), 10‐fold lower than the minimal effective concentration shown to promote Aβ clearance in vitro. Our studies suggest Cabernet Sauvignon exerts a beneficial effect by promoting nonamyloidogenic processing of amyloid precursor protein, which ultimately prevents the generation of Aβ peptides. This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia.—Wang, J., Ho, L., Zhao, Z., Seror, I., Humala, N., Dickstein, D. L., Meenakshisundaram, T., Percival, S. S., Talcott, S. T., Pasinetti, G. M. Moderate consumption of Cabernet Sauvignon attenuates Aβ neuropathology in a mouse model of Alzheimers disease. FASEB J. 20, 2313–2320 (2006)

Copper and immunity.

The immune system requires copper to perform several functions, of which little is known about the direct mechanism of action. Animal models and cells in culture have been used to assess coppers role in the immune response. Some of the recent research showed that interleukin 2 is reduced in copper deficiency and is likely the mechanism by which T cell proliferation is reduced. These results were extended to show that even in marginal deficiency, when common indexes of copper are not affected by the diet, the proliferative response and interleukin concentrations are reduced. The number of neutrophils in human peripheral blood is reduced in cases of severe copper deficiency. Not only are they reduced in number, but their ability to generate superoxide anion and kill ingested microorganisms is also reduced in both overt and marginal copper deficiency. This mechanism is not yet understood. Neutrophil-like HL-60 cells accumulate copper as they differentiate into a more mature cell population and this accumulation is not reflected by increases in Cu/Zn superoxide dismutase or cytochrome-c oxidase activities. The identity of copper-binding proteins in this cell type may be useful in learning new functions of copper or assessing copper status. Neutrophils, because they are short-lived and homogeneous cell populations, are predicted to be an effective and valuable tool for assessing nutrient status in human populations.

Use of Echinacea in medicine.

Echinacea, also known as the purple coneflower, is an herbal medicine that has been used for centuries, customarily as a treatment for the common cold, coughs, bronchitis, upper respiratory infections, and some inflammatory conditions. Research on echinacea, including clinical trials, is limited and largely in German. More information is needed before a definitive statement about the efficacy of echinacea can be made. Future work needs to clearly identify the species of echinacea and distinguish between the efficacy of the different plant parts (roots versus upper plant parts). Although many of the active compounds of echinacea have been identified, the mechanism of action is not known, nor is the bioavailability, relative potency, or synergistic effects of the active compounds known. Interpretation of existing literature suggests that echinacea should be used as a treatment for illness, not as a means for prevention of illness. The consensus of the studies reviewed in this article is that echinacea is indeed effective in reducing the duration and severity of symptoms, but that this effect is noted only with certain preparations of echinacea. Studies show that the plant and its active components affect the phagocytic immune system, but not the specifically acquired immune system.

Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer’s disease

Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimers disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain‐targeted polyphenols for potential beneficial AD disease‐modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle‐control treatment, one of the brain‐targeted polyphenol metabolites, quercetin‐3‐O‐glucuronide, significantly reduced the generation of β‐amyloid (Aβ) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain‐targeted metabolite, malvidin‐3‐O‐glucoside, had no detectable effect on Aβ generation. Moreover, in an in vitro analysis using the photo‐induced cross‐linking of unmodified proteins (PICUP) technique, we found that quercetin‐3‐O‐glucuronide is also capable of interfering with the initial protein‐protein interaction of Aβ1–40 and Aβ1–42 that is necessary for the formation of neurotoxic oligomeric Aβ species. Lastly, we found that quercetin‐3‐O‐glucuronide treatment, compared to vehicle‐control treatment, significantly improved AD‐type deficits in hippocampal formation basal synaptic transmission and long‐term potentiation, possibly through mechanisms involving the activation of the c‐Jun N‐terminal kinases and the mitogen‐activated protein kinase signaling pathways. Brain‐targeted quercetin‐3‐O‐glucuronide may simultaneously modulate multiple independent AD disease‐modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.—Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T.‐Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., Pasinetti, G. M. Identification of brain‐targeted bioactive dietary quercetin‐3‐O‐glucuronide as a novel intervention for Alzheimers disease. FASEB J. 27, 769–781 (2013). www.fasebj.org

Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study

OBJECTIVE Previous studies examining the effect of tea drinking on cardiovascular health have produced mixed results due to their observational nature and qualitatively and quantitatively imprecise definitions of active tea components. The objective of this study was to determine if a standardized and defined decaffeinated green tea (Camellia sinensis) product lowers blood pressure, serum lipids, oxidative stress, and markers of chronic inflammation. METHODS A randomized, double-blind, placebo-controlled, parallel study on 111 healthy adult volunteers 21-70 y old was performed. We administered a standardized capsule of Camellia sinensis compounds (CSC) twice a day. Before and after 3 wk, blood pressure, serum lipids, serum amyloid-alpha (a marker of chronic inflammation), and serum malondialdehyde (a marker of oxidative stress) were measured. RESULTS After 3 wk, CSC lowered systolic and diastolic blood pressures by 5 and 4 mmHg, respectively. After 3 mo, systolic blood pressure remained significantly lower. CSC lowered serum amyloid-alpha by 42% and lowered malondialdehyde by 11.9%. In men, there were 10- and 9-mg/dL reductions in total and low-density lipoprotein (LDL) cholesterol, respectively. In all subjects with a baseline LDL cholesterol level >99 mg/dL, there was 9 mg/dL lowering of total and LDL cholesterol. Adverse effects were mild and few and not different from placebo. CONCLUSION CSC was effective for decreasing, in as quickly as 3 wk, blood pressure, LDL cholesterol, oxidative stress, and a marker of chronic inflammation, all independent cardiovascular risk factors.

Specific Formulation of Camellia sinensis Prevents Cold and Flu Symptoms and Enhances γδ T Cell Function: A Randomized, Double-Blind, Placebo-Controlled Study

Objective: Determine if a specific formulation of Camellia sinensis (CSF) can prevent illness and symptoms due to cold and flu, and enhance γδ T cell function Methods: Design: Randomized, double-blind, placebo-controlled study. Subjects: Healthy adults 18–70 years old. Intervention: Proprietary formulation of Camellia sinensis (green tea) capsules, or a placebo, twice a day, for 3 months. Measures of Outcome: As assessed by daily symptom logs, percentage of subjects experiencing cold and flu symptoms, number of days subjects experienced symptoms, and percentage of subjects seeking medical treatment. Mean in vivo and ex vivo proliferative and interferon gamma responses of subjects’ peripheral blood mononuclear cells to γδ T cell antigen stimulation. Results: Among subjects taking CSF there were 32.1% fewer subjects with symptoms (P = 0.035), 22.9% fewer overall illnesses of at least 2 days duration (P = 0.092), and 35.6% fewer symptom days (P < 0.002), compared to subjects taking placebo. γδ T cells from subjects taking CSF proliferated 28% more (P = 0.017) and secreted 26% more IFN-γ (P = 0.046) in response to γδ T cell antigens, as compared to γδ T cells from subjects taking placebo. CSF was well-tolerated. Conclusions: This proprietary formulation of CSF is a safe and effective dietary supplement for preventing cold and flu symptoms, and for enhancing γδ T cell function.

Fabrication of nanoparticles using partially purified pomegranate ellagitannins and gelatin and their apoptotic effects

SCOPE Nanoparticles possess unique chemical and biological properties compared to bulk materials. Bioactive food components encapsulated in nanoparticles may have increased bioavailability and bioactivities. METHODS AND RESULTS Self-assembled nanoparticles made of partially purified pomegranate ellagitannins (PPE) and gelatin were fabricated using three PPE-to-gelatin mass ratios (1:5, 5:5, and 7:5). The PPE contained 16.6% (w/w) of punicalagin A, 32.5% (w/w) of punicalagin B, and a small amount of ellagic acid-hexoside and ellagic acid (1%, w/w). Nanoparticles fabricated using the ratio 5:5 had a particle size of 149.3±1.8 nm, positive zeta-potential of 17.8±0.9 mV, production efficiency 53.0±4.2%, and spherical morphology under scanning electron microscopy. Loading efficiency of punicalagin A and punicalagin B in these particles were 94.2±0.4% and 83.8±0.5 %, respectively. Loading capacity was 14.8±1.5% and 25.7±2.2%, respectively. Only punicalagin anomers were able to bind with gelatin to form nanoparticles, whereas ellagic acid-hexoside or ellagic acid could not. Fourier transform infrared spectroscopy suggested that the interactions between ellagitannins and gelatin were hydrogen bonding and hydrophobic interactions. PPE-gelatin nanoparticle suspension was less effective than PPE in inducing the early stage of apoptosis on human promyelocytic leukemia cells HL-60. But they had similar effects in inducing late stage of apoptosis and necrosis. CONCLUSION Pomegranate ellagitannins bind with gelatin to form self-assembled nanoparticles. Ellagitannins encapsulated in nanoparticles had decreased apoptotic effects on leukemia cells HL-60.

Transport of Cranberry A-Type Procyanidin Dimers, Trimers, and Tetramers across Monolayers of Human Intestinal Epithelial Caco-2 Cells

A-type procyanidin oligomers in cranberries are known to inhibit the adhesion of uropathogenic bacteria. B-type procyanidin dimers and trimers are absorbed by humans. The absorption of A-type procyanidins from cranberries in humans has not been demonstrated. This study examined the transport of A-type cranberry procyanidin dimers, trimers, and tetramers on differentiated human intestinal epithelial Caco-2 cell monolayers. Procyanidins were extracted from cranberries and purified using chromatographic methods. Fraction I contained predominantly A-type procyanidin dimer A2 [epicatechin-(2-O-7, 4-8)-epicatechin]. Fraction II contained primarily A-type trimers and tetramers, with B-type trimers, A-type pentamers, and A-type hexamers being minor components. Fraction I or II in solution was added onto the apical side of the Caco-2 cell membranes. The media at the basolateral side of the membranes were analyzed using HPLC-MS(n) after 2 h. Data indicated that procyanidin dimer A2 in fraction I and A-type trimers and tetramers in fraction II traversed across Caco-2 cell monolayers with transport ratio of 0.6%, 0.4%, and 0.2%, respectively. This study demonstrated that A-type dimers, trimers, and tetramers were transported across Caco-2 cells at low rates, suggesting that they could be absorbed by humans after cranberry consumption.

Grape Consumption Supports Immunity in Animals and Humans

All nutrients play a role in maintaining the immune system and providing substrate for the response. gammadelta T cells, on the other hand, seem to have a unique response to certain dietary bioactive components found in the plant family. Although the identification of those components is not well known yet, members of the proanthocyanidin family and the anthocyanin family of compounds are candidates. Because grapes and grape products contain both of these types of compounds, I hypothesized that grapes may help maintain or support the immune response, specifically the gammadelta T cell. Data from intact animal studies show that immune function is supported by grape products. In humans, relatively little research has been conducted using the food as an intervention; however, a study currently in progress showed that Concord grape juice supported circulating gammadelta T cells and maintained immune function, whereas participants receiving the placebo juice had changes associated with reduced immunity. After an overview of immunity, this paper will focus on reviewing the literature on grapes and other food products made from grapes and their potential for interaction with the gammadelta T cell in whole-body systems.

Pulsed Ultraviolet Light Reduces Immunoglobulin E Binding to Atlantic White Shrimp (Litopenaeus setiferus) Extract

Pulsed ultraviolet light (PUV), a novel food processing and preservation technology, has been shown to reduce allergen levels in peanut and soybean samples. In this study, the efficacy of using PUV to reduce the reactivity of the major shrimp allergen, tropomyosin (36-kDa), and to attenuate immunoglobulin E (IgE) binding to shrimp extract was examined. Atlantic white shrimp (Litopenaeus setiferus) extract was treated with PUV (3 pulses/s, 10 cm from light source) for 4 min. Tropomyosin was compared in the untreated, boiled, PUV-treated and [boiled+PUV]-treated samples, and changes in the tropomyosin levels were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). IgE binding of the treated extract was analyzed via immunoblot and enzyme-linked immunosorbent assay (ELISA) using pooled human plasma containing IgE antibodies against shrimp allergens. Results showed that levels of tropomyosin and IgE binding were reduced following PUV treatment. However, boiling increased IgE binding, while PUV treatment could offset the increased allergen reactivity caused by boiling. In conclusion, PUV treatment reduced the reactivity of the major shrimp allergen, tropomyosin, and decreased the IgE binding capacity of the shrimp extract.